This invention relates to .beta.-lactam antibiotics. In particular, it relates to chiral .beta.-lactam intermediates and to a process for the preparation thereof.
The penicillin and cephalosporin antibiotics can be considered as classical .beta.-lactam antibiotics. In recent years other monocyclic and bicyclic .beta.-lactam antibiotic compounds and .beta.-lactamase inhibitory compounds have been discovered such as the mono-bactams, clavulanic acid, thienamycin, and the 1-carba(1-dethia)cephalosporin compounds. Considerable effort has been devoted to the development of preparative methods for the synthesis of these nonclassical .beta.-lactam compounds. In particular, asymmetric preparative methods have undergone considerable study. Among the more efficient methods for constructing the .beta.-lactam ring is the so-called keteneimine cycloaddition comprising the reaction of an amino-protected glycyl chloride or other ketene generating derivative with an imine in the presence of a tertiary amine. For example, Evans et al., U.S. Pat. No. 4,665,171, describe an asymmetric method for preparing the .beta.-lactam ring which comprises the cycloaddition of an imine with a chiral 4-(S)-aryloxazolidin-2-one-3-yl acetyl halide wherein the aryloxazolidinone functions as the chiral auxiliary. According to the process of this invention, the chirality of the .beta.-lactam ring is induced with a chiral epoxyaldehyde employed to form the imine for use in the cycloaddition.